Microbicidal composition containing glutaraldehyde and orthophenylphenol

ABSTRACT

This invention relates to synergistic mixtures of orthophenolphenol and/or its sodium salt with glutaraldehyde and the use of the synergistic combinations in industrial applications.

This invention relates to synergistic mixtures of o-phenylphenol and/orits sodium salt with glutaraldehyde and the use of the synergisticcombinations in industrial applications.

O-phenylphenol and sodium orthophenylphenate (separately or collectivelyherein known as “OPP”, orthophenolphenol or o-phenylphenol and/or itssodium salt) are known and used extensively as antimicrobial agents invarious industrial applications such as preservation of variousmaterials including paints and adhesives as well as to control unwantedmicroorganisms found in various process waters such as cooling water,paper mills and petroleum production process waters.

The contamination of various products with microbiological growth hasled to the study and application of large classes of preservatives,antimicrobial compositions, and microbiocides to inhibit or prevent suchcontamination. Industrial process waters also have been studied andtreated extensively. Preservatives are used in a broad range of productsincluding but not limited to adhesives, cosmetics and toiletries,disinfectants and sanitizers, leather, metalworking fluids, paints andcoatings, plastics and resins, latex polymers, textiles and wood.Failure to preserve these products adequately will result in spoilageand loss of the materials to be preserved and will result in an economicloss. Similarly, microbiological growths can have dire consequences ifprocess waters are not adequately treated. Process waters include butare not limited to: industrial recirculating water, paper products(i.e., paper), petroleum production and leather tanning. Process watersare of concern because when fouled with biofilms that develop from theindigenous microbes present, bioflims may develop into thick gelatinouslike masses. Slime is produced by a wide range of bacteria, fungi, andyeast. Slime will interfere with the process resulting in a loss of heattransfer, corrosion and fouling.

Some of the microorganisms responsible for the extensive economiceffects described above have exhibited resilient resistant tendenciesagainst the standard and widely used microbiocides and antimicrobialcompositions, and accordingly the search for more effectiveantimicrobials has extended to a search for synergistic combinations ofmaterials considered to be relatively safe for humans. There remains aneed for combinations of materials of low or nonexistent toxicity tohumans which are effective against a wide range of microorganisms.

STATEMENT OF THE INVENTION

The present invention is directed to a microbicidal compositioncomprising: (a) orthophenolphenol; and (b) glutaraldehyde.

DETAILED DESCRIPTION OF THE INVENTION

As used herein, the following terms have the designated definitions,unless the context clearly indicates otherwise. “Orthophenolphenol”means O-phenylphenol and sodium orthophenylphenate (separately orcollectively herein known as “OPP”, orthophenolphenol or o-phenylphenoland/or its sodium salt or “SOPP”. In the present inventionorthophenolphenol is preferably orthophenylphenol in sodium salt form orSOPP. “Glutaraldehyde” means Pentane-1,5-dial (CAS Registry 111-30-8).The term “microbicide” is synonymous with “biocide” and refers to acompound capable of killing, inhibiting the growth of or controlling thegrowth of microorganisms at a locus; microbicides include bactericides,fungicides and algaecides. The term “microorganism” includes, forexample, fungi (such as yeast and mold), bacteria and algae, preferablybacteria. The term “locus” refers to an industrial system or productsubject to contamination by microorganisms. The following abbreviationsare used throughout the specification: ppm=parts per million by weight(weight/weight), mL=milliliter, ATCC=American Type Culture Collection,MBC=minimum biocidal concentration, and MIC=minimum inhibitoryconcentration. Unless otherwise specified, temperatures are in degreescentigrade (° C.), and references to percentages (%) are by weight.Amounts of organic microbicides are given on an active ingredient basisin ppm (w/w).

The compositions of the present invention unexpectedly have been foundto provide enhanced microbicidal efficacy at a combined activeingredient level lower than that of the individual microbicides.Additional microbicides beyond those listed in the claims may be presentin the composition.

The antimicrobial composition comprises glutaraldehyde andorthophenolphenol. A suitable weight ratio of glutaraldehyde toorthophenolphenol is from 1:2.2 to 1:28.7.

The microbicides in the composition of this invention may be used “asis” or may first be formulated with a solvent or a solid carrier.Suitable solvents include, for example, water; glycols, such as ethyleneglycol, propylene glycol, diethylene glycol, dipropylene glycol,polyethylene glycol, and polypropylene glycol; glycol ethers; alcohols,such as methanol, ethanol, propanol, phenethyl alcohol andphenoxypropanol; ketones, such as acetone and methyl ethyl ketone;esters, such as ethyl acetate, butyl acetate, triacetyl citrate, andglycerol triacetate; carbonates, such as propylene carbonate anddimethyl carbonate; and mixtures thereof. It is preferred that thesolvent is selected from water, glycols, glycol ethers, esters andmixtures thereof. Suitable solid carriers include, for example,cyclodextrin, silicas, diatomaceous earth, waxes, cellulosic materials,alkali and alkaline earth (e.g., sodium, magnesium, potassium) metalsalts (e.g., chloride, nitrate, bromide, and sulfate) and charcoal.

When a microbicide component is formulated in a solvent, the formulationmay optionally contain surfactants. When such formulations containsurfactants, they are generally in the form of emulsive concentrates,emulsions, microemulsive concentrates, or microemulsions. Emulsiveconcentrates form emulsions upon the addition of a sufficient amount ofwater. Microemulsive concentrates form microemulsions upon the additionof a sufficient amount of water. Such emulsive and microemulsiveconcentrates are generally well known in the art; it is preferred thatsuch formulations are free of surfactants. U.S. Pat. No. 5,444,078 maybe consulted for further general and specific details on the preparationof various microemulsions and microemulsive concentrates.

A microbicide component also can be formulated in the form of adispersion. The solvent component of the dispersion can be an organicsolvent or water, preferably water. Such dispersions can containadjuvants, for example, co-solvents, thickeners, anti-freeze agents,dispersants, fillers, pigments, surfactants, biodispersants,sulfosuccinates, terpenes, furanones, polycations, stabilizers, scaleinhibitors and anti-corrosion additives.

Those skilled in the art will recognize that the microbicide componentsof the present invention may be added to a locus sequentially,simultaneously, or may be combined before being added to the locus. Itis preferred that the first microbicide and the second microbicidecomponent be added to a locus simultaneously or sequentially. When themicrobicides are added simultaneously or sequentially, each individualcomponent may contain adjuvants, such as, for example, solvent,thickeners, anti-freeze agents, colorants, sequestrants (such asethylenediamine-tetraacetic acid, ethylenediaminedisuccinic acid,iminodisuccinic acid and salts thereof), dispersants, surfactants,biodispersants, sulfosuccinates, terpenes, furanones, polycations,stabilizers, scale inhibitors and anti-corrosion additives.

The microbicidal compositions of the present invention can be used toinhibit the growth of microorganisms or higher forms of aquatic life(such as protozoans, invertebrates, bryozoans, dinoflagellates,crustaceans, mollusks, etc.) by introducing a microbicidally effectiveamount of the compositions onto, into, or at a locus subject tomicrobial attack. Suitable loci include, for example: industrial processwater; electrocoat deposition systems,; cooling towers; air washers; gasscrubbers; mineral slurries; wastewater treatment; ornamental fountains;reverse osmosis filtration; ultrafiltration; ballast water; evaporativecondensers; heat exchangers; pulp and paper processing fluids andadditives; starch; plastics; emulsions; dispersions; paints; latices;coatings, such as varnishes; construction products, such as mastics,caulks, and sealants; construction adhesives, such as ceramic adhesives,carpet backing adhesives, and laminating adhesives; industrial orconsumer adhesives; photographic chemicals; printing fluids; householdproducts, such as bathroom and kitchen cleaners and sanitary wipes;cosmetics; toiletries; shampoos; soaps; detergents; industrial cleaners;floor polishes; laundry rinse water; metalworking fluids; conveyorlubricants; hydraulic fluids; leather and leather products; textiles;textile products; wood and wood products, such as plywood, chipboard,wallboard, flakeboard, laminated beams, oriented strandboard, hardboard,and particleboard; petroleum processing fluids; fuel; oilfield fluids,such as injection water, fracture fluids, and drilling muds; agricultureadjuvant preservation; surfactant preservation; medical devices;diagnostic reagent preservation; food preservation, such as plastic orpaper food wrap; food, beverage, and industrial process pasteurizers;toilet bowls; recreational water; pools; and spas.

Preferably, the microbicidal compositions of the present invention areused to inhibit the growth of microorganisms at a locus selected fromone or more of mineral slurries, pulp and paper processing fluids andadditives, starch, emulsions, dispersions, paints, latices, coatings,construction adhesives, such as ceramic adhesives, carpet backingadhesives, photographic chemicals, printing fluids, household productssuch as bathroom and kitchen cleaners and sanitary wipes, cosmetics,toiletries, shampoos, soaps, detergents, industrial cleaners, floorpolishes, laundry rinse water, metal working fluids, textile products,wood and wood products, agriculture adjuvant preservation, surfactantpreservation, diagnostic reagent preservation, food preservation, andfood, beverage, and industrial process pasteurizers.

The specific amount of the composition of this invention necessary toinhibit or control the growth of microorganisms and higher aquatic lifeforms in a locus depends upon the particular locus to be protected.Typically, the amount of the composition of the present invention tocontrol the growth of microorganisms in a locus is sufficient if itprovides from 0.1 to 1,000 ppm of the sodium orthophenolphenolingredient of the composition in the locus. It is preferred that thesodium orthophenolphenol ingredients of the composition be present inthe locus in an amount of at least 5 ppm, more preferably at least 10ppm and most preferably at least 20 ppm. It is preferred that the sodiumorthophenolphenol ingredients of the composition be present in the locusin an amount of no more than 0.8%, more preferably no more than 0.5%,and most preferably no more than 0.1%.

EXAMPLES Materials and Methods Biocides Used

Two biocides and their combinations were tested at differentconcentration ranges. These biocides are DOWICIDE A, and UCARCIDE 50.All biocide solutions were prepared and diluted in sterile DI water andused within 2 hours. These biocides are commercially available from TheDow Chemical Company.

TABLE 1 Biocides Commercial Biocides Active UCARCIDE 50 50%Glutaraldehyde DOWICIDE A 71.7% sodium orthophenylphenol

Bacterial Culture

TABLE 2 Bacterial cultures used for time kill test Bacteria Pseudomonasaeruginosa ATCC# 15442 Pseudomonas aeruginosa ATCC# 10145 Enterobacteraerogenes ATCC# 13048 Escherichia coli ATCC# 11229 Klebsiella pneumoniaeATCC# 8308 Staphylococcus aureus ATCC# 6538 Salmonella choleraesuisATTC# 10708

A bacteria pool was used for testing. 24 hr bacterial cultures wereobtained in TSB (Tryptic Soy Broth) media at 37° C. incubation for theseven organisms. The bacterial pool of seven organism was prepared bytaking equal parts of a 24 hour stationary phase aliquot from eachbacterial culture and mixing them together. The starting bacterialconcentration within the test sample is at 1×10⁶˜1×10⁷ CFU/ml.

Dow Time-Kill Test

The time-kill tests were carried out to determine the thresholdconcentration of the biocide products in a pH 7.4 hand dish-washingliquid. Tests were conducted in a 96-deep well block format using atotal sample volume of 600 ul for all evaluations. The hand dish-washingsample was pre-contaminated with the bacterial culture at the finalbacterial concentration of at 1×10⁶˜1×10 ⁷ CFU/ml. Biocides were thenadded into this bacterial suspension at various levels and mixedimmediately. The mixed samples were then incubated at 37° C. At 24 hrs,viable bacteria remaining in the hand dish-washing samples weredetermined by 1:10 serial dilutions, transferring 20 ul aliquot of eachsample into 180 ul TSB/Resazurin media. Triplicate tests were conducted.MPN method was used to determine the microbial concentration after 24hours incubation at 37° C.

The following table details the threshold concentration at 24 hours toachieve >=4 log bacterial count reduction of tested biocide.

TABLE 3 Concentration required to achieve >=4 Log bacterial countsreduction of tested biocides Time 24 h Glutaraldehyde 100 (“Glut”) aloneSOPP alone 358.5

Synergy Index

The synergism of the combination of the present invention wasdemonstrated by testing a wide range of concentrations and ratios of thecompounds.

One measure of synergism is the industrially accepted method describedby Kull, F. C.; Eisman, P. C.; Sylwestrowicz, H. D. and Mayer, R. L., inApplied Microbiology 9:538-541 (1961), using the ratio determined by theformula:

Q _(a) /Q _(A) +Q _(b) /Q _(B)=Synergy Index (“SI”)

wherein:

-   -   Q_(A)=concentration of compound A (first component) in ppm,        acting alone, which produced an end point (MIC of Compound A).    -   Q_(a)=concentration of compound A in ppm, in the mixture, which        produced an end point.    -   Q_(B)=concentration of compound B (second component) in ppm,        acting alone, which produced an end point (MIC of Compound B).    -   Q_(b)=concentration of compound B in ppm, in the mixture, which        produced an end point.

When the sum of Q_(a)/Q_(A) and Q_(b)/Q_(B) is greater than one,antagonism is indicated. When the sum is equal to one, additivity isindicated, and when less than one, synergism is demonstrated. The lowerthe SI, the greater the synergy shown by that particular mixture. Theminimum inhibitory concentration (MIC) of a microbicide is the lowestconcentration tested under a specific set of conditions that preventsthe growth of added microorganisms.

The test results for demonstration of synergy of the SOPP combinationsof the present invention are shown below in Tables 4 and 5. Each tableshows the specific combinations of SOPP and glutaraldehyde; resultsagainst the microorganisms tested at 24 hours; the end-point activity inppm for SOPP alone (Q_(B)), for glutaraldehyde alone (Q_(A)), for SOPPin the mixture (Q_(b)) and for the glutaraldehyde in the mixture(Q_(a)); the calculated SI value; and the range of synergistic ratiosfor each combination tested (glutaraldehyde/SOPP or A/B).

Ratios of the two biocides exhibiting synergy are presented in Tables 4and 5.

TABLE 4 Minimum Inhibitory Active Weight Concentration ratio of (ppm)Synergy Glut and SOPP Glut SOPP Index Bacterial Pool Glut alone 100 0SOPP alone 0.00 358.5 1:7.2 25 179.25 0.75 1:14.3 12.5 179.25 0.631:28.7 6,25 179.25 0.56

The synergistic effect of Glutaraldehyde to SOPP was demonstrated at theratio 1:7.2 to 1:28.7

TABLE 5 Minimum Inhibitory Active Weight Concentration ratio of (ppm)Synergy Glut and SOPP Glut SOPP Index Bacterial Pool Glut alone 100 0SOPP alone 0.00 358.5 1:2.2 50 107.55 0.80 1:4.3 25 107.55 0.55 1:8.612.5 107.55 0.43

The synergistic effect of Glutaraldehyde to SOPP was demonstrated at theratio of 1:2.2 to 1:8.6

1. A microbicidal composition comprising: (a) glutaraldehyde; and (b)orthophenolphenol.
 2. The microbicidal composition of claim 1 in whichthe weight ratio of glutaraldehyde to orthophenolphenol is from 1:2.2 to1:28.7.
 3. A method of inhibiting the growth of microorganismscomprising adding the composition of claim 1 into an: industrial processwater; electrocoat deposition systems,; cooling towers; air washers; gasscrubbers; mineral slurries; wastewater treatment; ornamental fountains;reverse osmosis filtration; ultrafiltration; ballast water; evaporativecondensers; heat exchangers; pulp and paper processing fluids andadditives; starch; plastics; emulsions; dispersions; paints; latices;coatings, construction products, construction adhesives, industrial orconsumer adhesives; photographic chemicals; printing fluids; householdproducts, cosmetics; toiletries; shampoos; soaps; detergents; industrialcleaners; floor polishes; laundry rinse water; metalworking fluids;conveyor lubricants; hydraulic fluids; leather and leather products;textiles; textile products; wood and wood products,; petroleumprocessing fluids; fuel; oilfield fluids; agriculture adjuvantpreservation; surfactant preservation; medical devices; diagnosticreagent preservation; food preservation; food, beverage, and industrialprocess pasteurizers; toilet bowls; recreational water; pools; and spas.